TY - JOUR
T1 - Iron as a central player and promising target in cancer progression
AU - Jung, Michaela
AU - Mertens, Christina
AU - Tomat, Elisa
AU - Brüne, Bernhard
N1 - Funding Information:
This work was supported by the Deutsche Forschungsgemeinschaft (SFB815, project A8 (B.B.)), the Wilhelm Sander-Stiftung (2017.130.1 (M.J.)), and the US National Institutes of Health (GM127646 (E.T.)).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/1/2
Y1 - 2019/1/2
N2 - Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.
AB - Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.
KW - Iron chelators
KW - Iron homeostasis
KW - Lipocalin-2
KW - Macrophage polarization
KW - Tumor progression
UR - http://www.scopus.com/inward/record.url?scp=85060024672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060024672&partnerID=8YFLogxK
U2 - 10.3390/ijms20020273
DO - 10.3390/ijms20020273
M3 - Review article
C2 - 30641920
AN - SCOPUS:85060024672
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 2
M1 - 273
ER -